several step process. First, a patient’s tumor has to be sequenced. Then clinicians have to figure out which neo-antigens are the important ones. Then those neo-antigens have to be synthesized, and a vaccine developed. And then that vaccine has to be taken back to the patient and administered. “That’s the product. It’s not a simple drug in a bottle. You can’t just go to a contract manufacturer and say make me 40 kg of drug x, y, or z,” he said. “Doing this on a commercial scale is something that we’re going to continue to work through.”
—Battling the placebo effect with biomarkers. Two weeks ago, a drug Forum Pharmaceuticals has been developing for a variety of neurological diseases failed two Phase 3 studies in schizophrenia. It was tough news for Forum, which announced a restructuring as a result. “The trials read out with an enormous pro-cognitive effect across all groups—including the placebo,” Forum CEO Deborah Dunsire said at our event. “So here we are with a large set of trials done and this amazingly positive effect, but not separating our drug from placebo—and the question is, why is that?”
Indeed, despite numerous efforts and even some innovative clinical trial designs, the placebo effect is notorious for dooming a number of trials in psychiatric drugs; combating it is an enormous challenge for the field. Dunsire cited the lack of effective biomarkers as a critical problem, making it harder to identify the real responders. In Alzheimer’s, for instance, companies can use imaging technologies to detect the presence of amyloid clumps in the brain. Despite the fact that there hasn’t yet been an approved drug that reduces amyloid plaques, these technologies mean you can at least “image and see a response” to a drug, she said. In psychiatric diseases like depression or schizophrenia, by comparison, “we’re not really able to do that effectively yet,” which is making trials more unpredictable, Dunsire said.
“In neurology, we’re making progress,” she said. “In psychiatry, we’re at the very beginning and there’s a long way to go.”
—Gilead prevailed in a NASH bidding war. Last week, Gilead Sciences agreed to acquire an early-stage drug Cambridge, MA-based Nimbus Therapeutics has been developing for a liver disease called nonalcoholic steatohepatitis, or NASH. According to CEO Don Nicholson, the $1.2 billion bid from Gilead—which included $400 million up front—wasn’t the highest offer on the table. Furthermore, Nimbus didn’t originally intend to sell the program. It started meeting with investors to raise a crossover round, with an IPO in sight. “We have a vision of building a robust mid size biotech,” he said, which means doing everything from discovering drugs to selling them.
What Nicholson found, however, was pharma companies were becoming very interested in the NASH drug. So much so that various offers began to emerge—four in total—and Nimbus instead began to focus on a deal. One offer was an outright acquisition of the drug (Gilead), while the others were licensing deals and option-to-acquire agreements. Nicholson didn’t say which other bidders emerged, or who had actually outbid Gilead. But Nimbus chose Gilead for two reasons. First, the deal was an acquisition—which made sense given Nimbus’s LLC structure, as I explained in this post on the buyout last Monday. Second, since the deal included hundreds of millions of dollars in downstream payments, Nimbus wanted to pick who it thought would have the best chance to advance the drug far enough to trigger those payments.
“Gilead’s forte is in liver diseases, and it has a clear commitment to NASH,” Nicholson said. “Now they’ll have four clinical programs in NASH, which will enable combinations and all sorts of other things.”
—Cambridge must be a “convergence” hub. As a co-founder of Biogen, Phil Sharp has seen Cambridge become one of biotech’s epicenters first hand. It became that way, he said, because of “seeds” planted in the 1950s by Harvard University and MIT scientists that would put those institutions at the forefront of molecular biology germinated some 20 years later.
Sharp believes another critical time is upon Cambridge again. There is a “convergence” movement underway connecting a variety of disciplines once deemed separate—engineering, physical and computational science, life sciences, and otherwise. This type of convergence is at the heart of a number of broad biomedical efforts, among them President Obama’s precision medicine initiative, which combines elements of big data, genomics, and biomedical research. Synthetic biology, too, combines biology and engineering. (Here’s more on convergence via a paper Sharp and colleagues published in 2011.)
Sharp says this convergence is reflected by the fact that “like a herd of elephants,” large IT companies like Google and IBM have stormed in to Cambridge to set up outposts, aiming to make engineering “integral” to how we analyze biomedical problems. Now it’s up to all the members of the Cambridge biotech community—from companies to scientists on down—to take advantage, break down silos, work together, and lead the movement.
“If we let this get away from us we really need to be kicked in the you know what,” Sharp said.
—The problem with direct-to-consumer marketing: it works. Ironwood Pharmaceuticals CEO Peter Hecht and Dartmouth College professor Tillman Gerngross hosted a town hall-style forum on drug pricing, which elicited a lively back-and-forth between the two and many members of the audience passionate about everything from pricing models to the public image of biotech and pharma companies.
Hecht noted, for instance, that despite the fact that drug companies develop products that save and/or change people’s lives, the sector is “perceived to be a horrible industry, let’s not sugarcoat it.” One participant brought up the massive dollar figures drug companies spend on marketing as a reason for peoples’ distaste with pharma. “It just seems too much,” the attendee said.
“And unfortunately, it still works,” countered Hecht, who cited his company’s own experience selling the gastrointestinal drug linaclotide (Linzess). Hecht noted that Ironwood tried every way possible other than TV ads to get the word out about linaclotide. Ironwood did “the best digital outreach that’s ever been done in pharma,” yet Hecht said only a small percentage of patients were aware of the drug after it launched. Since it started TV ads over a million patients in the U.S. have taken linaclotide. “It’s a really tricky problem. You can like it or not like it, but [TV ads are] really effective,” he said.
